Description: (Applicant's Description) The objective of this sub-program of the NCDDG is the discovery of natural products that display promising activity in Wyeth Ayerst Research (W-AR) molecular target assays. The main emphasis will be on secondary metabolites of marine invertebrates, primarily sponges, and marine microorganisms associated with the marine sponges. Secondary metabolites from terrestrial plants and lichens endemic to Sri Lanka will provide an additional unique pool of chemical diversity. The specific aims to accomplish this goal are: . To collect marine invertebrates, primarily sponges, from tropical habitats in Papua New Guinea, Dominica, Indonesia, and Sri Lanka, and from cold water habitats in Canada, Brazil, and the Isle of Man. It is anticipated that in excess of 2,000 species of marine invertebrates will be collected over the duration of the granting period. All work on Brazilian and Sri Lankan marine invertebrate samples will be accomplished as part of subcontracts with the University of Sao Paulo and the University of Colombo, respectively. . To help W-AR scientists isolate microorganisms in the field from sponge and other invertebrate samples collected by Andersen group divers. . To collect endemic Sri Lankan plants and lichens. This will be accomplished as part of a subcontract with the University of Colombo. It is estimated that 1,750 species of plants/lichens will be collected. . To isolate pure active metabolites from extracts of the organisms mentioned above using bioassay-guided fractionation and to elucidate their chemical structures. To isolate sufficient quantities of promising new lead compounds from marine sponge and other invertebrate extracts, marine microbial fermentations, and Sri Lankan plants and lichens for in vivO evaluation in animal models at W-AR.